KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection.

Giulia Accardi, Gabriele Di Lorenzo, Raffaella Rubino, Claudia Colomba, Lydia Giannitrapani, Antonino Tuttolomondo, Calogero Caruso, Anna Aiello, Giuseppe Montalto, Antonio Cascio, Giuseppina Candore, Sergio Rizzo, Massimo Bilancia, Danilo Di Bona, Macchia, Giovanni Duro, Caiaffa, Candore, Sergio Rizzo, Calogero Caruso

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21 Citations (Scopus)

Abstract

Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P< 0.001), and HC (10%) (crude OR,12.38; P< 0.001). Similar results were obtained for the HLA-C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P< 0.10), and HC (60%) (crude OR, 3.56; P< 0.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR,0.10; P< 0.05). These results suggest a detrimental role of HLA-A-Bw4 and HLA-C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%), and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection
Original languageEnglish
Pages (from-to)768-775
Number of pages8
JournalJournal of Viral Hepatitis
Volume24
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases
  • Virology

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